Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions
Ankyrins together with their spectrin partners are the master organizers of micron-scale membrane domains in diverse tissues. The 24 ankyrin (ANK) repeats of ankyrins bind to numerous membrane proteins, linking them to spectrin-based cytoskeletons at specific membrane microdomains. The accessibility...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/29150 |
| _version_ | 1811200596230799360 |
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| author | Keyu Chen Jianchao Li Chao Wang Zhiyi Wei Mingjie Zhang |
| author_facet | Keyu Chen Jianchao Li Chao Wang Zhiyi Wei Mingjie Zhang |
| author_sort | Keyu Chen |
| collection | DOAJ |
| description | Ankyrins together with their spectrin partners are the master organizers of micron-scale membrane domains in diverse tissues. The 24 ankyrin (ANK) repeats of ankyrins bind to numerous membrane proteins, linking them to spectrin-based cytoskeletons at specific membrane microdomains. The accessibility of the target binding groove of ANK repeats must be regulated to achieve spatially defined functions of ankyrins/target complexes in different tissues, though little is known in this regard. Here we systemically investigated the autoinhibition mechanism of ankyrin-B/G by combined biochemical, biophysical and structural biology approaches. We discovered that the entire ANK repeats are inhibited by combinatorial and quasi-independent bindings of multiple disordered segments located in the ankyrin-B/G linkers and tails, suggesting a mechanistic basis for differential regulations of membrane target bindings by ankyrins. In addition to elucidating the autoinhibition mechanisms of ankyrins, our study may also shed light on regulations on target bindings by other long repeat-containing proteins. |
| first_indexed | 2024-04-12T02:06:08Z |
| format | Article |
| id | doaj.art-cddae088a0e247cf867d728a23f93dc7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:06:08Z |
| publishDate | 2017-08-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-cddae088a0e247cf867d728a23f93dc72022-12-22T03:52:31ZengeLife Sciences Publications LtdeLife2050-084X2017-08-01610.7554/eLife.29150Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regionsKeyu Chen0https://orcid.org/0000-0003-0321-0604Jianchao Li1https://orcid.org/0000-0002-8921-1626Chao Wang2Zhiyi Wei3https://orcid.org/0000-0002-4446-6502Mingjie Zhang4https://orcid.org/0000-0001-9404-0190Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, ChinaDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, ChinaDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, ChinaDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China; Department of Biology, South University of Science and Technology of China, Shenzhen, ChinaDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China; Center of Systems Biology and Human Health, Institute for Advanced Study, Hong Kong University of Science and Technology, Hong Kong, ChinaAnkyrins together with their spectrin partners are the master organizers of micron-scale membrane domains in diverse tissues. The 24 ankyrin (ANK) repeats of ankyrins bind to numerous membrane proteins, linking them to spectrin-based cytoskeletons at specific membrane microdomains. The accessibility of the target binding groove of ANK repeats must be regulated to achieve spatially defined functions of ankyrins/target complexes in different tissues, though little is known in this regard. Here we systemically investigated the autoinhibition mechanism of ankyrin-B/G by combined biochemical, biophysical and structural biology approaches. We discovered that the entire ANK repeats are inhibited by combinatorial and quasi-independent bindings of multiple disordered segments located in the ankyrin-B/G linkers and tails, suggesting a mechanistic basis for differential regulations of membrane target bindings by ankyrins. In addition to elucidating the autoinhibition mechanisms of ankyrins, our study may also shed light on regulations on target bindings by other long repeat-containing proteins.https://elifesciences.org/articles/29150Ankyrin-R/B/Gankyrin repeatsautoinhibitionaxon initial segment |
| spellingShingle | Keyu Chen Jianchao Li Chao Wang Zhiyi Wei Mingjie Zhang Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions eLife Ankyrin-R/B/G ankyrin repeats autoinhibition axon initial segment |
| title | Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions |
| title_full | Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions |
| title_fullStr | Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions |
| title_full_unstemmed | Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions |
| title_short | Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions |
| title_sort | autoinhibition of ankyrin b g membrane target bindings by intrinsically disordered segments from the tail regions |
| topic | Ankyrin-R/B/G ankyrin repeats autoinhibition axon initial segment |
| url | https://elifesciences.org/articles/29150 |
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